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DDX1 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 1)

Written2010-06Takahiko Hara, Kiyoko Tanaka
Stem cell project group, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_namesDEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 1
DEAD (Asp-Glu-Ala-Asp) box polypeptide 1
DEAD (Asp-Glu-Ala-Asp) box helicase 1
Alias_symbol (synonym)DBP-RB
Other aliasUKVH5d
HGNC (Hugo) DDX1
LocusID (NCBI) 1653
Atlas_Id 40283
Location 2p24.3  [Link to chromosome band 2p24]
Location_base_pair Starts at 15731745 and ends at 15771235 bp from pter ( according to hg19-Feb_2009)  [Mapping DDX1.png]
Fusion genes
(updated 2016)
CAMK2G (10q22.2) / DDX1 (2p24.3)DDX1 (2p24.3) / RPL28 (19q13.42)GABRB3 (15q12) / DDX1 (2p24.3)
HARS2 (5q31.3) / DDX1 (2p24.3)LAP3 (4p15.32) / DDX1 (2p24.3)NBAS (2p24.3) / DDX1 (2p24.3)
RNU6ATAC (9q34.2) / DDX1 (2p24.3)

DNA/RNA

 
  Genomic organization of human DDX1 gene. Boxes and connecting lines indicate exons (omitted in the middle part) and introns, respectively. The ATG transcription initiation site is located in exon 2.
Description DDX1 gene is located in an approximately 40 kb chromosomal DNA region of 2p24.3 containing at least 27 exons. There are alternatively used exons for exon 2, 16, 19, 21, 23 and 27.
Transcription Size of the major mRNA is 2.7 kb.

Protein

 
  Diagram of conserved motifs among DEAD box RNA helicase family proteins.
Description DDX1 protein is a putative RNA helicase containing the characteristic Asp-Glu-Ala-Asp (DEAD) conserved sequence motif (Linder et al., 1989). It is composed of 740 amino acid residues (82432 Da). Proteins of this family (more than 30 from bacteria to humans) have been described to be implicated in a number of cellular processes involving alteration of RNA secondary structure such as translational initiation, nuclear and mitochondrial RNA splicing, and ribosome/spliceosome assembly (Rocak and Linder, 2004).
Expression DDX1 mRNA is widely expressed in many tissues, but its expression level is highest in testis (Tanaka et al., 2009). DDX1 level tends to be higher in tumor-derived cells than in normal tissues.
Localisation DDX1 protein is localized both in the cytoplasm and nucleus of DDX1 gene-amplified neuroblastoma and retinoblastoma cell lines, but mainly located in the nucleus of normal fibroblasts (Godbout et al., 1998).
Function DDX1 is believed to regulate translational initiation, nuclear hnRNA splicing, ribosome/spliceosome assembly, and mRNA synthesis as a putative ATP-dependent RNA helicase. DDX1 is associated with a pre-mRNA 3'-end cleavage protein CstF-64 (Bleoo et al., 2001) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Chen et al., 2002). hnRNP-K is involved in cell migration and cytoplasmic accumulation of hnRNP-K is crucial for metastasis (Inoue et al., 2007). It was reported that DDX1 interacts with nuclear diffusion inhibitory signal (NIS) motif of HIV-1 Rev protein in human astrocytes. Accumulation of DDX1 in astrocytes changed sub-cellular distribution of Rev from nuclear to cytoplasmic (Fang et al., 2005). More recently, it was reported that DDX1 is recruited to the sites of DNA double strand breaks in cells exposed to ionizing radiation and removes single stranded RNAs to facilitate the repair reaction of transcriptionally active regions of the genome (Li et al., 2008).
In retinoblastoma and neuroblastoma cell lines, co-amplification of DDX1 and the proto-oncogene MYCN has been demonstrated (Godbout and Squire, 1993; Godbout et al., 1998). Similar gene amplification of the genomic region containing DDX1 and MYCN was observed in alveolar rhabdomyosarcoma samples (Barr et al., 2009) and Wilms tumor-derived cells (Noguera et al., 2010). Elevated expression of DDX1 mRNA was reported to be a prognostic marker for early recurrence in primary breast cancer (Germain et al., 2010).
Recently, it was demonstrated that DDX1 is essential for the solid tumor formation of a human testicular tumor cell line NEC8 in nude mice (Tanaka et al., 2009). In this case, DDX1 directly bound to the -348 and -329 promoter region of the cyclin-D2 gene and enhanced its transcription. Furthermore, siRNA-mediated knockdown of DDX1 resulted in coordinated down-regulation of stem cell-associated genes located in chromosomal region 12p13. Therefore, DDX1 may function as an essential transcriptional activator for the tumorigenic capacity of testicular germ line tumor-derived cells. In agreement, DDX1 promotes the proliferation of JC virus via the transcriptional activation of its viral promoter (Sunden et al., 2007). It was also reported that DDX1 acts as a co-activator to enhance NF-kappaB-mediated transcription (Ishaq et al., 2009).

Implicated in

Note
  
Entity Retinoblastoma and neuroblastoma
Note Coamplication of DDX1 and MYCN genes frequently occurs in both retinoblastoma and neuroblastoma cell lines. This is because DDX1 gene is located to chromosome 2p24, 400-kb telomeric to MYCN gene. This type of gene amplification has also been reported in alveolar rhabdomyosarcoma samples and Wilms tumor-derived cells. However, prognostic significance of the DDX1 gene amplification for the clinical outcome is not clear.
  
  
Entity Testicular tumors
Note In testicular tumors including seminoma and nonseminoma, significantly higher levels of DDX1 mRNA are expressed. In a nonseminoma-derived cell line NEC8, siRNA-mediated knockdown of DDX1 abrogated their anchorage-independent growth in a semisolid medium and in vivo tumor formation in nude mice.
  
  
Entity Breast cancer
Note Expression of DDX1 mRNA and cytoplasmic DDX1 levels are significantly elevated in relapsed breast cancer samples. Thus, DDX1 can be a prognostic biomarker for early recurrence in primary breast cancer.
  

Bibliography

Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group.
Barr FG, Duan F, Smith LM, Gustafson D, Pitts M, Hammond S, Gastier-Foster JM.
Genes Chromosomes Cancer. 2009 Aug;48(8):661-72.
PMID 19422036
 
Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA.
Bleoo S, Sun X, Hendzel MJ, Rowe JM, Packer M, Godbout R.
Mol Biol Cell. 2001 Oct;12(10):3046-59.
PMID 11598190
 
An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K.
Chen HC, Lin WC, Tsay YG, Lee SC, Chang CJ.
J Biol Chem. 2002 Oct 25;277(43):40403-9. Epub 2002 Aug 14.
PMID 12183465
 
The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes.
Fang J, Acheampong E, Dave R, Wang F, Mukhtar M, Pomerantz RJ.
Virology. 2005 Jun 5;336(2):299-307.
PMID 15892970
 
DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer.
Germain DR, Graham K, Glubrecht DD, Hugh JC, Mackey JR, Godbout R.
Breast Cancer Res Treat. 2010 May 25. [Epub ahead of print]
PMID 20499159
 
Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines.
Godbout R, Packer M, Bie W.
J Biol Chem. 1998 Aug 14;273(33):21161-8.
PMID 9694872
 
Amplification of a DEAD box protein gene in retinoblastoma cell lines.
Godbout R, Squire J.
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7578-82.
PMID 7689221
 
Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis.
Inoue A, Sawata SY, Taira K, Wadhwa R.
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8983-8. Epub 2007 May 4.
PMID 17483488
 
The DEAD-box RNA helicase DDX1 interacts with RelA and enhances nuclear factor kappaB-mediated transcription.
Ishaq M, Ma L, Wu X, Mu Y, Pan J, Hu J, Hu T, Fu Q, Guo D.
J Cell Biochem. 2009 Feb 1;106(2):296-305.
PMID 19058135
 
A role for DEAD box 1 at DNA double-strand breaks.
Li L, Monckton EA, Godbout R.
Mol Cell Biol. 2008 Oct;28(20):6413-25. Epub 2008 Aug 18.
PMID 18710941
 
Birth of the D-E-A-D box.
Linder P, Lasko PF, Ashburner M, Leroy P, Nielsen PJ, Nishi K, Schnier J, Slonimski PP.
Nature. 1989 Jan 12;337(6203):121-2.
PMID 2563148
 
Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line.
Noguera R, Villamon E, Berbegall A, Machado I, Giner F, Tadeo I, Navarro S, Llombart-Bosch A.
Diagn Mol Pathol. 2010 Mar;19(1):33-9.
PMID 20186010
 
DEAD-box proteins: the driving forces behind RNA metabolism.
Rocak S, Linder P.
Nat Rev Mol Cell Biol. 2004 Mar;5(3):232-41. (REVIEW)
PMID 14991003
 
DDX1 promotes proliferation of the JC virus through transactivation of its promoter.
Sunden Y, Semba S, Suzuki T, Okada Y, Orba Y, Nagashima K, Umemura T, Sawa H.
Microbiol Immunol. 2007;51(3):339-47.
PMID 17380054
 
DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes.
Tanaka K, Okamoto S, Ishikawa Y, Tamura H, Hara T.
Oncogene. 2009 May 28;28(21):2142-51. Epub 2009 Apr 27.
PMID 19398953
 

Citation

This paper should be referenced as such :
Hara, T ; Tanaka, K
DDX1 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(3):259-261.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DDX1ID40283ch2p24.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Nervous system: Peripheral neuroblastic tumours (Neuroblastoma, Ganglioneuroblastoma, Ganglioneuroma)
Head and neck: Retinoblastoma


External links

Nomenclature
HGNC (Hugo)DDX1   2734
Cards
AtlasDDX1ID40283ch2p24
Entrez_Gene (NCBI)DDX1  1653  DEAD/H-box helicase 1
AliasesDBP-RB; UKVH5d
GeneCards (Weizmann)DDX1
Ensembl hg19 (Hinxton)ENSG00000079785 [Gene_View]  chr2:15731745-15771235 [Contig_View]  DDX1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000079785 [Gene_View]  chr2:15731745-15771235 [Contig_View]  DDX1 [Vega]
ICGC DataPortalENSG00000079785
TCGA cBioPortalDDX1
AceView (NCBI)DDX1
Genatlas (Paris)DDX1
WikiGenes1653
SOURCE (Princeton)DDX1
Genetics Home Reference (NIH)DDX1
Genomic and cartography
GoldenPath hg19 (UCSC)DDX1  -     chr2:15731745-15771235 +  2p24   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)DDX1  -     2p24   [Description]    (hg38-Dec_2013)
EnsemblDDX1 - 2p24 [CytoView hg19]  DDX1 - 2p24 [CytoView hg38]
Mapping of homologs : NCBIDDX1 [Mapview hg19]  DDX1 [Mapview hg38]
OMIM601257   
Gene and transcription
Genbank (Entrez)AB593031 AB593032 AB593033 AB593034 AK297432
RefSeq transcript (Entrez)NM_004939
RefSeq genomic (Entrez)NC_000002 NC_018913 NT_005334 NW_004929298
Consensus coding sequences : CCDS (NCBI)DDX1
Cluster EST : UnigeneHs.440599 [ NCBI ]
CGAP (NCI)Hs.440599
Alternative Splicing GalleryENSG00000079785
Gene ExpressionDDX1 [ NCBI-GEO ]   DDX1 [ EBI - ARRAY_EXPRESS ]   DDX1 [ SEEK ]   DDX1 [ MEM ]
Gene Expression Viewer (FireBrowse)DDX1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1653
GTEX Portal (Tissue expression)DDX1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ92499   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ92499  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ92499
Splice isoforms : SwissVarQ92499
Catalytic activity : Enzyme3.6.4.13 [ Enzyme-Expasy ]   3.6.4.133.6.4.13 [ IntEnz-EBI ]   3.6.4.13 [ BRENDA ]   3.6.4.13 [ KEGG ]   
PhosPhoSitePlusQ92499
Domaine pattern : Prosite (Expaxy)B302_SPRY (PS50188)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    Q_MOTIF (PS51195)   
Domains : Interpro (EBI)B30.2/SPRY    ConA-like_dom    DEAD/DEAH_box_helicase_dom    Helicase_ATP-bd    Helicase_C    P-loop_NTPase    RNA_helicase_DEAD_Q_motif    SPRY_dom   
Domain families : Pfam (Sanger)DEAD (PF00270)    Helicase_C (PF00271)    SPRY (PF00622)   
Domain families : Pfam (NCBI)pfam00270    pfam00271    pfam00622   
Domain families : Smart (EMBL)DEXDc (SM00487)  HELICc (SM00490)  SPRY (SM00449)  
Conserved Domain (NCBI)DDX1
DMDM Disease mutations1653
Blocks (Seattle)DDX1
PDB (SRS)4XW3   
PDB (PDBSum)4XW3   
PDB (IMB)4XW3   
PDB (RSDB)4XW3   
Structural Biology KnowledgeBase4XW3   
SCOP (Structural Classification of Proteins)4XW3   
CATH (Classification of proteins structures)4XW3   
SuperfamilyQ92499
Human Protein AtlasENSG00000079785
Peptide AtlasQ92499
HPRD03158
IPIIPI00293655   IPI01010287   IPI00893677   
Protein Interaction databases
DIP (DOE-UCLA)Q92499
IntAct (EBI)Q92499
FunCoupENSG00000079785
BioGRIDDDX1
STRING (EMBL)DDX1
ZODIACDDX1
Ontologies - Pathways
QuickGOQ92499
Ontology : AmiGOspliceosomal complex assembly  DNA binding  chromatin binding  transcription cofactor activity  RNA helicase activity  double-stranded RNA binding  ATP-dependent RNA helicase activity  nuclease activity  exonuclease activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  double-strand break repair  transcription, DNA-templated  regulation of transcription, DNA-templated  tRNA splicing, via endonucleolytic cleavage and ligation  tRNA splicing, via endonucleolytic cleavage and ligation  regulation of translational initiation  multicellular organism development  ATP-dependent helicase activity  poly(A) binding  response to virus  cytoplasmic stress granule  RNA secondary structure unwinding  membrane  intracellular ribonucleoprotein complex  DNA duplex unwinding  DNA/RNA helicase activity  response to exogenous dsRNA  poly(A) RNA binding  cleavage body  tRNA-splicing ligase complex  nucleic acid phosphodiester bond hydrolysis  nucleic acid phosphodiester bond hydrolysis  protein localization to cytoplasmic stress granule  
Ontology : EGO-EBIspliceosomal complex assembly  DNA binding  chromatin binding  transcription cofactor activity  RNA helicase activity  double-stranded RNA binding  ATP-dependent RNA helicase activity  nuclease activity  exonuclease activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  double-strand break repair  transcription, DNA-templated  regulation of transcription, DNA-templated  tRNA splicing, via endonucleolytic cleavage and ligation  tRNA splicing, via endonucleolytic cleavage and ligation  regulation of translational initiation  multicellular organism development  ATP-dependent helicase activity  poly(A) binding  response to virus  cytoplasmic stress granule  RNA secondary structure unwinding  membrane  intracellular ribonucleoprotein complex  DNA duplex unwinding  DNA/RNA helicase activity  response to exogenous dsRNA  poly(A) RNA binding  cleavage body  tRNA-splicing ligase complex  nucleic acid phosphodiester bond hydrolysis  nucleic acid phosphodiester bond hydrolysis  protein localization to cytoplasmic stress granule  
REACTOMEQ92499 [protein]
REACTOME Pathways6784531 [pathway]   
NDEx NetworkDDX1
Atlas of Cancer Signalling NetworkDDX1
Wikipedia pathwaysDDX1
Orthology - Evolution
OrthoDB1653
GeneTree (enSembl)ENSG00000079785
Phylogenetic Trees/Animal Genes : TreeFamDDX1
HOVERGENQ92499
HOGENOMQ92499
Homologs : HomoloGeneDDX1
Homology/Alignments : Family Browser (UCSC)DDX1
Gene fusions - Rearrangements
Fusion : MitelmanCAMK2G/DDX1 [10q22.2/2p24.3]  [t(2;10)(p24;q22)]  
Fusion : MitelmanLAP3/DDX1 [4p15.32/2p24.3]  [t(2;4)(p24;p15)]  
Fusion : MitelmanNBAS/DDX1 [2p24.3/2p24.3]  [t(2;2)(p24;p24)]  
Fusion: TCGALAP3 4p15.32 DDX1 2p24.3 BLCA
Fusion: TCGANBAS 2p24.3 DDX1 2p24.3 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDDX1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DDX1
dbVarDDX1
ClinVarDDX1
1000_GenomesDDX1 
Exome Variant ServerDDX1
ExAC (Exome Aggregation Consortium)DDX1 (select the gene name)
Genetic variants : HAPMAP1653
Genomic Variants (DGV)DDX1 [DGVbeta]
DECIPHER (Syndromes)2:15731745-15771235  ENSG00000079785
CONAN: Copy Number AnalysisDDX1 
Mutations
ICGC Data PortalDDX1 
TCGA Data PortalDDX1 
Broad Tumor PortalDDX1
OASIS PortalDDX1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDDX1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDDX1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch DDX1
DgiDB (Drug Gene Interaction Database)DDX1
DoCM (Curated mutations)DDX1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DDX1 (select a term)
intoGenDDX1
NCG5 (London)DDX1
Cancer3DDDX1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601257   
Orphanet
MedgenDDX1
Genetic Testing Registry DDX1
NextProtQ92499 [Medical]
TSGene1653
GENETestsDDX1
Huge Navigator DDX1 [HugePedia]
snp3D : Map Gene to Disease1653
BioCentury BCIQDDX1
ClinGenDDX1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1653
Chemical/Pharm GKB GenePA27199
Clinical trialDDX1
Miscellaneous
canSAR (ICR)DDX1 (select the gene name)
Probes
Litterature
PubMed92 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDDX1
EVEXDDX1
GoPubMedDDX1
iHOPDDX1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:30:26 CEST 2017

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